AU2014331628B2 - Inhibitors of ERK and methods of use - Google Patents
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- AU2014331628B2 AU2014331628B2 AU2014331628A AU2014331628A AU2014331628B2 AU 2014331628 B2 AU2014331628 B2 AU 2014331628B2 AU 2014331628 A AU2014331628 A AU 2014331628A AU 2014331628 A AU2014331628 A AU 2014331628A AU 2014331628 B2 AU2014331628 B2 AU 2014331628B2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| CN109761986B (zh) * | 2017-11-10 | 2021-10-08 | 上海翰森生物医药科技有限公司 | 三并环类衍生物抑制剂、其制备方法和应用 |
| CN107879989B (zh) * | 2017-11-29 | 2020-01-03 | 重庆市中药研究院 | 具有生物活性的3,4,5-取代苯并二氮卓2-酮类药物分子及其制备方法 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014179154A2 (en) * | 2013-04-30 | 2014-11-06 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
Family Cites Families (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3657744A (en) | 1970-05-08 | 1972-04-25 | Univ Minnesota | Method for fixing prosthetic implants in a living body |
| BE791816R (fr) | 1971-11-24 | 1973-05-23 | Sandoz Sa | Derives de la quinazolinone, leur preparation et medicaments contenant ces |
| US3984556A (en) * | 1973-01-19 | 1976-10-05 | Sandoz, Inc. | Alkyl-substituted-tricyclic quinazolinones for lowering blood pressure |
| US4042704A (en) | 1976-03-18 | 1977-08-16 | Sandoz, Inc. | Benzindazoles |
| US4352931A (en) | 1980-05-22 | 1982-10-05 | Siegfried Aktiengesellschaft | Lin-benzoaminopurinols |
| US4733665C2 (en) | 1985-11-07 | 2002-01-29 | Expandable Grafts Partnership | Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US5061273A (en) | 1989-06-01 | 1991-10-29 | Yock Paul G | Angioplasty apparatus facilitating rapid exchanges |
| US5350395A (en) | 1986-04-15 | 1994-09-27 | Yock Paul G | Angioplasty apparatus facilitating rapid exchanges |
| US5040548A (en) | 1989-06-01 | 1991-08-20 | Yock Paul G | Angioplasty mehtod |
| US4748982A (en) | 1987-01-06 | 1988-06-07 | Advanced Cardiovascular Systems, Inc. | Reinforced balloon dilatation catheter with slitted exchange sleeve and method |
| DE3701277A1 (de) * | 1987-01-17 | 1988-07-28 | Boehringer Mannheim Gmbh | Neue tricyclische benzimidazole, verfahren zu ihrer herstellung und verwendung als arzneimittel |
| US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
| CA1322628C (en) | 1988-10-04 | 1993-10-05 | Richard A. Schatz | Expandable intraluminal graft |
| GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
| US6344053B1 (en) | 1993-12-22 | 2002-02-05 | Medtronic Ave, Inc. | Endovascular support device and method |
| US5674278A (en) | 1989-08-24 | 1997-10-07 | Arterial Vascular Engineering, Inc. | Endovascular support device |
| US5292331A (en) | 1989-08-24 | 1994-03-08 | Applied Vascular Engineering, Inc. | Endovascular support device |
| US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
| IL112248A0 (en) * | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
| US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
| DK0821671T3 (da) | 1995-04-20 | 2001-04-23 | Pfizer | Arylsulfonylhydroxamsyrederivater som MMP- og TNF-inhibitorer |
| DE69624081T2 (de) | 1995-12-20 | 2003-06-12 | Agouron Pharmaceuticals, Inc. | Matrix-metalloprotease Inhibitoren |
| EP0923585B1 (en) | 1996-07-18 | 2002-05-08 | Pfizer Inc. | Phosphinate based inhibitors of matrix metalloproteases |
| WO1998007697A1 (en) | 1996-08-23 | 1998-02-26 | Pfizer Inc. | Arylsulfonylamino hydroxamic acid derivatives |
| WO1998030566A1 (en) | 1997-01-06 | 1998-07-16 | Pfizer Inc. | Cyclic sulfone derivatives |
| EP0977733B1 (en) | 1997-02-03 | 2003-09-03 | Pfizer Products Inc. | Arylsulfonylamino hydroxamic acid derivatives |
| JP2000507975A (ja) | 1997-02-07 | 2000-06-27 | ファイザー・インク | N−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用 |
| EA002546B1 (ru) | 1997-02-11 | 2002-06-27 | Пфайзер Инк. | Производные арилсульфонилгидроксамовой кислоты |
| GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
| GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
| PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
| PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
| US6087368A (en) | 1998-06-08 | 2000-07-11 | Bristol-Myers Squibb Company | Quinazolinone inhibitors of cGMP phosphodiesterase |
| US6562836B1 (en) * | 1999-05-24 | 2003-05-13 | Queen's University Of Kingston | Methods and compounds for inhibiting amyloid deposits |
| EP1317450B1 (en) | 2000-09-15 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| JP3896309B2 (ja) * | 2001-07-09 | 2007-03-22 | ファイザー株式会社 | プロテインキナーゼc阻害物質としてのピラゾロキノリノン誘導体 |
| US7119111B2 (en) | 2002-05-29 | 2006-10-10 | Amgen, Inc. | 2-oxo-1,3,4-trihydroquinazolinyl derivatives and methods of use |
| AR045595A1 (es) | 2003-09-04 | 2005-11-02 | Vertex Pharma | Composiciones utiles como inhibidores de proteinas quinasas |
| US20050203063A1 (en) * | 2003-09-12 | 2005-09-15 | Raymond Deshaies | Proteasome pathway inhibitors and related methods |
| US7244757B2 (en) | 2004-04-01 | 2007-07-17 | Pfizer Inc | Pyrazole-amine compounds for the treatment of neurodegenerative disorders |
| US7384930B2 (en) | 2004-11-03 | 2008-06-10 | Bristol-Myers Squibb Company | Constrained compounds as CGRP-receptor antagonists |
| MX2008010635A (es) | 2006-02-16 | 2008-10-28 | Schering Corp | Derivados de pirrolidina como inhibidores de cinasa regulada por señales extracelulares. |
| AR068046A1 (es) | 2007-06-05 | 2009-11-04 | Schering Corp | Derivados policiclicos de indazol y su uso como inhibidores de erk para el tratamiento del cancer |
| WO2008156739A1 (en) | 2007-06-18 | 2008-12-24 | Schering Corporation | Heterocyclic compounds and use thereof as erk inhibitors |
| DK2217597T3 (da) | 2007-10-01 | 2011-06-20 | Comentis Inc | Quinuclidin-4-ylmethyl-1h-indol-3-carboxylatderivater som alpha-7-nicotin-acetylcholin-receptor-ligander til behandling af Alzheimers sygdom |
| WO2009105500A1 (en) | 2008-02-21 | 2009-08-27 | Schering Corporation | Compounds that are erk inhibitors |
| US8022227B2 (en) | 2008-08-27 | 2011-09-20 | The Ohio State University | Method of synthesizing 1H-indazole compounds |
| EP2408448A4 (en) | 2009-03-18 | 2012-09-19 | Univ Leland Stanford Junior | METHODS AND COMPOSITIONS FOR TREATING INFECTION WITH A FLAVIVIRIDAE FAMILY VIRUS |
| SI2455381T1 (sl) * | 2009-07-17 | 2014-08-29 | Japan Tobacco Inc. | Triazolopiridinova spojina in njeno delovanje kot zaviralec prolil-hidroksilaze in induktor produkcije eritropoietina |
| JP2013506669A (ja) | 2009-09-30 | 2013-02-28 | メルク・シャープ・アンド・ドーム・コーポレーション | Erk阻害剤である新規化合物 |
| WO2012030685A2 (en) | 2010-09-01 | 2012-03-08 | Schering Corporation | Indazole derivatives useful as erk inhibitors |
| US9242981B2 (en) | 2010-09-16 | 2016-01-26 | Merck Sharp & Dohme Corp. | Fused pyrazole derivatives as novel ERK inhibitors |
| EP3536319A1 (en) | 2010-10-29 | 2019-09-11 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
| EP2654748B1 (en) | 2010-12-21 | 2016-07-27 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as erk inhibitors |
| WO2012170845A2 (en) * | 2011-06-08 | 2012-12-13 | Heffernan Michele L R | Metabotropic glutamate receptor 5 modulators and methods of use thereof |
| EP2770987B1 (en) | 2011-10-27 | 2018-04-04 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
| WO2014052566A1 (en) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
| WO2014052563A2 (en) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
| WO2014134772A1 (en) | 2013-03-04 | 2014-09-12 | Merck Sharp & Dohme Corp. | Compounds inhibiting leucine-rich repeat kinase enzyme activity |
| EP3363800A1 (en) | 2013-10-03 | 2018-08-22 | Kura Oncology, Inc. | Heterocyclic inhibitors of erk and methods of use |
| WO2016095089A1 (en) | 2014-12-15 | 2016-06-23 | Merck Sharp & Dohme Corp. | Erk inhibitors |
| WO2016095088A1 (en) | 2014-12-15 | 2016-06-23 | Merck Sharp & Dohme Corp. | Erk inhibitors |
| CN107001322B (zh) | 2014-12-18 | 2020-07-28 | 默沙东公司 | 用于药物制剂的组合物 |
| MX2017008078A (es) | 2014-12-19 | 2017-09-28 | Merck Sharp & Dohme | Composiciones de (s)-n-(3-(6-isopropoxipiridin-3-il)-1h-indazol-5- il)-1-(2-(4-(4-(1-metil-1h-1,2,4-triazol-3-il)fenil)-3,6-dihidrop iridin-1(2h)-il)-2-oxoetil)-3-(metiltio)pirrolidin-3-carboxamida para preparaciones farmaceuticas. |
| TWI704151B (zh) | 2014-12-22 | 2020-09-11 | 美商美國禮來大藥廠 | Erk抑制劑 |
-
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2014179154A2 (en) * | 2013-04-30 | 2014-11-06 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
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